rs468646

Variant names:

• chr21-41437279-A-C
• rs468646
• NM_002462.5:c.436+127A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-41437279-A-C
• chr21-41437279-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002462.5(MX1):​c.436+127A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 969,452 control chromosomes in the GnomAD database, including 96,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (12139 hom., cov: 31)
  • Exomes 𝑓: 0.43 (84219 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 5 publications found

Genes affected

MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	NM_002462.5	MANE Select	c.436+127A>C		intron	N/A	NP_002453.2	P20591-1
	MX1	NM_001144925.2		c.436+127A>C		intron	N/A	NP_001138397.1	P20591-1
	MX1	NM_001178046.3		c.436+127A>C		intron	N/A	NP_001171517.1	P20591-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MX1	ENST00000398598.8	TSL:1 MANE Select	c.436+127A>C		intron	N/A	ENSP00000381599.3	P20591-1
	MX1	ENST00000455164.6	TSL:1	c.436+127A>C		intron	N/A	ENSP00000410523.2	P20591-1
	MX1	ENST00000896042.1		c.436+127A>C		intron	N/A	ENSP00000566101.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56557 AN: 151902 Hom.: 12142 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.430 AC: 351289 AN: 817432 Hom.: 84219 AF XY: 0.427 AC XY: 178305 AN XY: 418028

African (AFR) AF: 0.199 AC: 4018 AN: 20166

American (AMR) AF: 0.242 AC: 6954 AN: 28680

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 5156 AN: 16302

East Asian (EAS) AF: 0.00376 AC: 137 AN: 36470

South Asian (SAS) AF: 0.265 AC: 14661 AN: 55252

European-Finnish (FIN) AF: 0.475 AC: 20544 AN: 43276

Middle Eastern (MID) AF: 0.317 AC: 1346 AN: 4252

European-Non Finnish (NFE) AF: 0.493 AC: 283441 AN: 574960

Other (OTH) AF: 0.395 AC: 15032 AN: 38074

GnomAD4 genome AF: 0.372 AC: 56573 AN: 152020 Hom.: 12139 Cov.: 31 AF XY: 0.367 AC XY: 27302 AN XY: 74302

African (AFR) AF: 0.215 AC: 8937 AN: 41474

American (AMR) AF: 0.308 AC: 4702 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3472

East Asian (EAS) AF: 0.00715 AC: 37 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4824

European-Finnish (FIN) AF: 0.483 AC: 5092 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34016 AN: 67938

Other (OTH) AF: 0.370 AC: 779 AN: 2104

Alfa AF: 0.430 Hom.: 9618

Bravo AF: 0.350

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs468646; hg19: chr21-42809206; COSMIC: COSV55819146; COSMIC: COSV55819146;